Abstract
Many observational studies have identified a link between Epstein-Barr virus (EBV) and stomach conditions, such as gastric cancer (GC). This study investigated the causal relationship between EBV and GC and conditions that may lead to GC, such as gastritis and gastric ulcer. Data regarding GC were sourced from a FINN cohort; data regarding EBV were obtained from a previous study that relied on the UK Biobank cohort. Inverse-variance weighted (IVW) was used as a primary analysis; Mendelian randomization-Egger (MR-Egger), Weighted median (WM), and weighted model were applied to validate the robustness of the results. MR-Egger regression method was used to explore the presence of horizontal pleiotropy, and the MR pleiotropy residual sum and outlier (MR-PRESSO) method was applied to detect potential outliers. Cochran's Q test was used to test heterogeneity among instrumental variables (IVs). Genetic prediction linked EBV EBNA-1 antibody levels significantly with GC and gastritis, unaffected by horizontal pleiotropy. MR-PRESSO found no outliers for EBNA-1 and GC, but two for gastritis. Heterogeneity was noted in anti-EBV IgG and peptic ulcer, and EBNA-1 and VCA p18 antibodies for gastritis. The present MR analysis provides evidence supporting a causal role for genetically predicted EBNA-1 antibody levels in the etiology of GC. Taking EBV infection into account could help tailor the screening and diagnosis of GC to each patient.